Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity
Document Type
Article
Abstract
Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the same rapamycin treatment reported to extend mouse life span significantly impaired glucose homeostasis of aged mice. Moreover, rapamycin treatment of lean C57B/L6 mice reduced glucose-stimulated insulin secretion in vivo and ex vivo as well as the insulin content and beta cell mass of pancreatic islets. Confounding the diminished capacity for insulin release, rapamycin decreased insulin sensitivity. The multitude of rapamycin effects thus all lead to glucose intolerance. As our findings reveal that chronic rapamycin treatment could be diabetogenic, monitoring glucose homeostasis is crucial when using rapamycin as a therapeutic as well as experimental reagent. © Springer-Verlag 2012.
Keywords
Diabetes, Glucose intolerance, Insulin, MTOR, Rapamycin
Publication Date
5-1-2012
Publication Title
Journal of Molecular Medicine
ISSN
09462716
E-ISSN
14321440
Volume
90
Issue
5
First Page
575
Last Page
585
PubMed ID
22105852
Digital Object Identifier (DOI)
10.1007/s00109-011-0834-3
Recommended Citation
Yang, Shi Bing; Lee, Hye Young; Young, David Matthew; Tien, An Chi; Rowson-Baldwin, Ashley; Shu, Yu Yu; Jan, Yuh Nung; and Jan, Lily Yeh, "Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity" (2012). Translational Neuroscience. 2008.
https://scholar.barrowneuro.org/neurobiology/2008